In a series of studies, we and others have found that patients with schizophrenia have relatively reduced metabolic rates in their frontal cortex when assessed with positron emission tomography imaging with 18-F 2-deoxyglucose (FDG). We proposed to extend these results with four studies to assess the effects of neuroleptic medication, to examine never-medicated patients, to explore frontal lobe function in additional patients with affective disorder, and to characterize the attentional deficit of patients showing relative hypofrontality. In Experiment 1, 24 patients with schizophrenia will participate in a 12-week trial of a standard neuroleptic; the design will be a double-blind, random assignment crossover with PET scans after each 6-week period. In experiment 2, 24 never-medicated patients will be scanned for comparison with off-medication patients already tested to examine potential medication artifacts. In experiment 3, 24 patients with major affective disorder, 12 bipolar and 12 unipolar, will be scanned. In experiment 4, PET scans on a memory-load but non-degraded stimulus CPT will be compared in normals and schizophrenics to further assess right lateralization seen in the current series. Patients will be evaluated clinically with an expanded lifetime version of the Present State exam structured interview, diagnosed by DSM-III criteria, and screened for medical illness. Non- prescription drug use will be assessed by urine testing. Subjects will perform the Continuous Performance Test during FDG uptake. Following uptake of FDG and labeling of brain structures in the psychophysical laboratory, the NeuroEcat scanner (7.6 mm in plane and 11.6 mm axial resolution) will obtain slice images to assess the metabolic rate of glucose. PET images will be converted to units of micromoles glucose/100g/minute and analyzed quantitatively. All subjects will receive MRI scans using the same individually fitted, thermoplastic head holder to allow specific structures to be identified by reference to the anatomic image. Multivariate analyses of frontal cortex and basal ganglia metabolic rates will evaluate drug effects and group differences to test specific hypotheses.